Compositions including polymerizable bisphosphonic acids and methods

ABSTRACT

The present invention is directed to compositions containing one or more polymerizable bisphosphonic acids and optionally one or more additional polymerizable components.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority to U.S. ProvisionalPatent Application Serial No. 60/437,106, filed on Dec. 30, 2002, whichis incorporated herein by reference.

TECHNICAL FIELD

[0002] The present invention is directed toward compositions containingpolymerizable bisphosphonic acids that can be used in a variety ofapplications, particularly medical, dental, and orthodonticapplications, for example. Such compositions are particularly useful asetchants, especially self-etching primers and self-etching adhesives, topromote adhesion of dental restoratives, orthodontic appliances, etc.,to dental structures.

BACKGROUND

[0003] The restoration of decayed dental structures including caries,decayed dentin or decayed enamel, is often accomplished by thesequential application of a dental adhesive and then a dental material(e.g., a restorative material) to the relevant dental structures.Similarly, adhesives are used in the bonding of orthodontic appliances(generally also utilizing an orthodontic adhesive) to a dentalstructure. Often various pretreatment processes are used to promote thebonding of adhesives to dentin or enamel, for example. Typically, suchpretreatment steps include etching using, for example, inorganic ororganic acids, followed by priming to improve the bonding between thetooth structure and the overlying adhesive.

[0004] Whether for application of dental restoratives (e.g., composites,fillings, sealants, inlays, onlays, crowns, bridges, etc.) ororthodontic appliances to a tooth structure, the etchants, primers, andadhesives are typically applied in a step-wise fashion. Often betweensuch steps, one or more rinsing and drying steps are used. As a result,dental restoration and the application of orthodontic appliancestypically involve multi-step procedures.

[0005] To simplify conventional restorative and/or orthodonticprocedures, for example, it would be desirable to provide a singlecomposition that accomplishes both etching and priming. Thus, there is aneed for a self-etching primer, particularly a self-etching dentalprimer, for improved bonding of an adhesive (e.g., a dental adhesive) toa substrate surface (e.g., dental structure, such as dentin, enamel,bone, or other hard tissue) and that could eliminate the conventionalpost-etching rinsing and drying steps. Furthermore, there is still aneed for new compositions that can serve as self-etching adhesives,i.e., a single-composition adhesive with priming and etching propertiesthat can be applied in a single pretreatment step. Preferred embodimentsof the present invention meet some of these needs.

SUMMARY

[0006] The present invention is directed to compositions containing oneor more polymerizable bisphosphonic acids, salts thereof, orcombinations thereof. Such compositions are useful in a variety ofmedical and dental applications, for example, as etchants, particularlyself-etching primers (i.e., etchant/primer compositions). Thesecompositions can be used in methods and kits for improving the bondingof adhesives (and subsequently the adherence of a material, e.g., adental restorative or an orthodontic appliance) to a hard surface,preferably, to at least one type of medical structure or dentalstructure. Preferably, compositions of the present invention alsofunction as self-etching adhesives (i.e., etchant/primer/adhesivecompositions).

[0007] The compositions of the present invention include one or morepolymerizable bisphosphonic acids of Formula I, or more particularly,one or more polymerizable bisphosphonic acids of Formula II. Suchcompounds can be in their acid form (as shown) or in their salt form.

[0008] In the compounds of Formula I: R¹ is an organic group thatincludes a polymerizable group; and R² is H, OR, SR, N(R)₂, or anorganic group that can optionally join with R¹ to form a carbon-carbondouble bond with the carbon between the two phosphorus atoms (i.e., theR¹ and R² groups are one and the same with a C═C bond), wherein theorganic group optionally includes a polymerizable group, and furtherwherein each R is independently hydrogen or an organic group optionallyincluding a polymerizable group. In any one compound, the R groups maybe the same or different.

[0009] In the compounds of Formula II: x=1-3; R² is H, OH, an alkylgroup, an aryl group, an alkoxy group, an aryloxy group, or-A-(N(R⁴)—C(O)—C(R³)═CH₂)_(x); each R³ is independently H or CH₃; eachR⁴ is H, an alkyl group, or can be joined to A forming a cyclic organicgroup; and A is a bond or a straight chain or branched organic group. Inany one compound, the groups -A-(N(R⁴)—C(O)—C(R³)═CH₂)_(x) may be thesame or different.

[0010] Preferably, the polymerizable bisphosphonic acid is present in anamount of at least about 1 percent by weight (wt-%), more preferably, atleast about 5 wt-%, based on the total weight of the composition.

[0011] For certain preferred embodiments, A of Formula II is a straightchain or branched organic group when the composition includes apolymerizable component that is different from the compound of FormulaII and is otherwise formulated for use as an etchant, more preferably aself-etching primer or a self-etching adhesive, which is particularlyuseful on hard tissue.

[0012] For certain preferred embodiments, A of Formula II is a bond or astraight chain or branched organic group when the composition includes apolymerizable component that is different from the compound of FormulaII and the compound of Formula II is present in an amount of at leastabout 1 wt-%, based on the total weight of the composition.

[0013] Certain preferred embodiments of the compositions of the presentinvention are self-etching primers, thereby being capable of etching andpriming a hard surface, particularly a tooth surface, simultaneously.Alternatively, a separate dental primer can be used if desired.

[0014] Certain preferred embodiments of the compositions of the presentinvention are self-etching adhesives, which can, for example, promoteadherence of a dental material (e.g., a composite, a filling, a sealant,an inlay, an onlay, a crown, and a bridge) to the tooth surface.Alternatively, a separate dental adhesive can be used if desired.

[0015] Certain methods of the present invention involve treating a hardsurface that includes etching the hard surface with a composition of thepresent invention with the proviso that the hard surface is notpretreated.

[0016] The compositions of the present invention can function to promotethe adherence of an orthodontic adhesive to the tooth surface, whereinthe orthodontic adhesive functions to adhere an orthodontic appliance tothe tooth surface. Thus, certain methods of the present inventioninvolve adhering an orthodontic appliance (e.g., a bracket, a buccaltube, a band, a cleat, a button, a lingual retainer, and a bite blocker)to the tooth surface after the tooth surface has been etched by acomposition including a polymerizable bisphosphonic acid.

[0017] In certain preferred methods, an orthodontic adhesive is adheredto the tooth surface, which can optionally be pre-applied to theorthodontic appliance before adhering to the tooth surface. The methodcan also optionally include a step of priming the tooth surface prior toadhering an orthodontic appliance to the tooth surface. If thecomposition further includes at least one polymerizable componentdifferent from the polymerizable bisphosphonic acid, the steps ofetching and priming are done simultaneously with the compositionfunctioning as a self-etching primer composition. The method can alsooptionally include a step of applying a dental adhesive to the toothsurface prior to adhering an orthodontic appliance to the tooth surface.If the composition further includes at least one polymerizable componentdifferent from the polymerizable bisphosphonic acid, the steps ofetching and applying a dental adhesive are done simultaneously with thecomposition acting as a self-etching adhesive composition. For certainembodiments, the methods of the present invention can include adheringan orthodontic adhesive to the tooth surface, wherein preferably theorthodontic adhesive has been pre-applied to the orthodontic appliancebefore adhering to the tooth surface.

[0018] Definitions:

[0019] Herein, “adhesive” or “dental adhesive” refers to a compositionused as a pre-treatment on a dental structure (e.g., a tooth) to adherea “dental material” (e.g., “restorative”), an orthodontic appliance(e.g., bracket), or an “orthodontic adhesive” to the dental structure.An “orthodontic adhesive” refers to a highly (generally greater than 40%by weight) filled composition (more analogous to a “restorativematerial” than to a “dental adhesive”) used to adhere an orthodonticappliance to a dental structure (e.g., tooth) surface. Generally, thetooth surface is pre-treated, e.g., by etching, priming, and/or applyingan adhesive to enhance the adhesion of the “orthodontic adhesive” to thetooth surface. “Dental structures” refer to tooth structures (e.g.,enamel and dentin) and bone, for example.

[0020] The terms “comprises” and variations thereof do not have alimiting meaning where these terms appear in the description and claims.

[0021] As used herein, “a,” “an,” “the,” “at least one,” and “one ormore” are used interchangeably.

[0022] Also herein, the recitations of numerical ranges by endpointsinclude all numbers subsumed within that range (e.g., 1 to 5 includes 1,1.5, 2, 2.75, 3, 3.80, 4, 5, etc.).

[0023] The above summary of the present invention is not intended todescribe each disclosed embodiment or every implementation of thepresent invention. The description that follows more particularlyexemplifies illustrative embodiments. In several places throughout theapplication, guidance is provided through lists of examples, whichexamples can be used in various combinations. In each instance, therecited list serves only as a representative group and should not beinterpreted as an exclusive list.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0024] The present invention is directed to compositions containing oneor more polymerizable bisphosphonic acids. Herein, when bisphosphonicacids are mentioned, this includes the acid form, salts thereof, orcombinations thereof. Preferably, the compositions also include one ormore additional polymerizable components.

[0025] The compositions of the present invention are useful for treatinghard surfaces, preferably, hard tissues such as dentin, enamel, andbone. Although the compositions of the present invention areparticularly desirable for use on at least one type of medical structure(e.g., bone, cartilage, medical instruments) or dental structure (e.g.,dentin, enamel, or bone), they can be used to etch, preferably etch andprime, hard surfaces such as metal and metal oxide surfaces. Thecompositions of the present invention are typically used with anoverlying adhesive (e.g., a dental adhesive), but they can be used asthe adhesive (i.e., a self-etching adhesive) in certain preferredembodiments.

[0026] Thus, compositions of the present invention are useful asetchants for hard surfaces. In certain preferred embodiments, thecompositions are self-etching primers. That is, they can etch and primea surface in one step, thereby eliminating conventional post-etchingrinsing and drying steps. An adhesive is then applied over the etchedand primed surface. In certain other preferred embodiments, thecompositions are self-etching adhesives. That is, they etch and prime asurface in one step and function as an adhesive.

[0027] Such self-etching primer and self-etching adhesive compositionsare typically prepared by the addition of one or more polymerizablecomponents to a bisphosphonic acid compound. The selection of additionalpolymerizable components is made to impart the desired priming and/oradhesive properties to the compositions. Generally, techniques forselecting polymerizable components and optional other components toimpart priming and/or adhesive properties to hard-surface treatmentcompositions are well known to those skilled in formulation of dentaland medical materials. Suitable polymerizable components for use in suchcompositions, as well as conventional dental primers and dentaladhesives that can be incorporated into the compositions, or usedseparately but in combination with the compositions, are discussedherein. Alternatively, priming and/or adhesive properties may beimparted to the composition by chemical modification of thebisphosphonic acid(s) without the addition of other polymerizablecomponents to the composition.

[0028] The compositions of the present invention are preferably used topromote the adhesion of a material (e.g., a dental restorative ororthodontic appliance) to a hard surface, particularly a tooth surface(e.g., enamel or dentin). Typically, the compositions are hardened(i.e., polymerized by conventional photopolymerization and/or chemicalpolymerization techniques) prior to adherence of the material. It issignificant if the composition can be formulated to promote adhesion toboth enamel and dentin. It is particularly significant if thecomposition can be formulated to function as the etchant, primer, andadhesive to both enamel and dentin.

[0029] The compositions of the present invention can be used to promotethe adhesion of dental restoratives (e.g., composites, fillings,sealants, inlays, onlays, crowns, bridges) or orthodontic appliances(e.g., brackets (optionally precoated with orthodontic adhesives),buccal tubes, bands, cleats, buttons, lingual retainers, and biteblockers) to dental structures.

[0030] In addition to the polymerizable bisphosphonic acid and otheroptional polymerizable components, the compositions of the presentinvention optionally can include fillers, solvents, dental adhesives,and/or dental primers. Various combinations of the components describedherein can be used in the compositions of the present invention.

[0031] Certain preferred aqueous-based embodiments (i.e., includingwater in the composition) of the present invention are self-etchingprimer and self-etching adhesive compositions with enhanced hydrolyticstability, e.g., having a room-temperature shelf-life stability of atleast 1 year, and preferably at least 2 years. Additionally, preferredcompositions, especially self-etching adhesive compositions, do notrequire any pre-mixing steps prior to application to the surface of thedental structure.

[0032] Bisphosphonic Acids and Salts Thereof

[0033] The polymerizable bisphosphonic acids are of the followingformula (Formula I):

[0034] or a salt thereof, wherein: R¹ is an organic group that includesa polymerizable group; and R² is H, OR, SR, N(R)₂, or an organic groupthat can optionally join with R¹ to form a carbon-carbon double bondwith the carbon between the two phosphorus atoms, wherein the organicgroup optionally includes a polymerizable group, and further whereineach R is independently hydrogen or an organic group optionallyincluding a polymerizable group. In the case where R¹ and R² join toform a double bond, that double bond can be the polymerizable group ofR¹.

[0035] Preferably, the polymerizable group is an ethylenicallyunsaturated group. More preferably, the ethylenically unsaturated groupis a (meth)acrylate group, a (meth)acrylamido group, or a vinyl group.

[0036] A particularly preferred class of polymerizable bisphosphonicacids is of the following formula (Formula II):

[0037] or a salt thereof, wherein: x=1-3 (preferably, x is 1-2, and morepreferably, 1); R² is H, OH, an alkyl group, an aryl group, an alkoxygroup, an aryloxy group, or -A-(N(R⁴)C(O)C(R³)═CH₂)_(x); each R³ isindependently H or CH₃ (i.e, an acrylamido group or a methacrylamidogroup, often referred to as a (meth)acrylamido group); each R⁴ isindependently H, an alkyl group, or can be joined to A forming a cyclicorganic group; and A is a bond or a straight chain or branched organicgroup. When x is 2 or 3, preferably, the ethylenically unsaturatedgroups (x) are not bonded to the same carbon atom of A. They can bepresent in their acid form or their salt form. Thus, when a compound ofFormulas I or II or other bisphosphonic acids of the present inventionare referred to herein, they encompass both acids and salts.

[0038] Preferably, a polymerizable bisphosphonic acid compound of thepresent invention is present in a composition in an amount effective toetch hard tissue. Typically, this is an amount of at least about 1percent by weight (wt-%), based on the total weight of the composition.More preferably, a polymerizable bisphosphonic acid compound of thepresent invention is present in an amount of at least about 5 wt-%,based on the total weight of the composition. If more than onepolymerizable bisphosphonic acid compound is used, these amounts applyto the total amount of the mixture.

[0039] In the formulas for the bisphosphonic acid compounds describedherein, the term “organic group” means a hydrocarbon group (withoptional elements other than carbon and hydrogen, such as oxygen,nitrogen, sulfur, phosphorus, and silicon) that is classified as analiphatic group, cyclic group, or combination of aliphatic and cyclicgroups (e.g., alkaryl and aralkyl groups). In the context of the presentinvention, the organic groups are those that do not interfere with theformation of an etchant for a hard surface. The term “aliphatic group”means a saturated or unsaturated linear or branched hydrocarbon group.This term is used to encompass alkyl, alkenyl, and alkynyl groups, forexample. The term “alkyl group” means a saturated linear or branchedhydrocarbon group including, for example, methyl, ethyl, isopropyl,t-butyl, heptyl, dodecyl, octadecyl, amyl, 2-ethylhexyl, and the like.The term “alkenyl group” means an unsaturated, linear or branchedhydrocarbon group with one or more carbon-carbon double bonds, such as avinyl group. The term “alkynyl group” means an unsaturated, linear orbranched hydrocarbon group with one or more carbon-carbon triple bonds.The term “cyclic group” means a closed ring hydrocarbon group that isclassified as an alicyclic group, aromatic group, or heterocyclic group.The term “alicyclic group” means a cyclic hydrocarbon group havingproperties resembling those of aliphatic groups. The term “aromaticgroup” or “aryl group” means a mono- or polynuclear aromatic hydrocarbongroup. The term “heterocyclic group” means a closed ring hydrocarbon inwhich one or more of the atoms in the ring is an element other thancarbon (e.g., nitrogen, oxygen, sulfur, etc.).

[0040] Substitution is anticipated on the organic groups of thepolymerizable bisphosphonic acid compounds of the present invention. Asa means of simplifying the discussion and recitation of certainterminology used throughout this application, the terms “group” and“moiety” are used to differentiate between chemical species that allowfor substitution or that may be substituted and those that do not allowor may not be so substituted. Thus, when the term “group” is used todescribe a chemical substituent, the described chemical materialincludes the unsubstituted group and that group with O, N, Si, P, or Satoms, for example, in the chain (as in an alkoxy group) as well ascarbonyl groups or other conventional substitution. Where the term“moiety” is used to describe a chemical compound or substituent, only anunsubstituted chemical material is intended to be included. For example,the phrase “alkyl group” is intended to include not only pure open chainsaturated hydrocarbon alkyl substituents, such as methyl, ethyl, propyl,t-butyl, and the like, but also alkyl substituents bearing furthersubstituents known in the art, such as hydroxy, alkoxy, alkylsulfonyl,halogen atoms, cyano, nitro, amino, carboxyl, etc. Thus, “alkyl group”includes ether groups, haloalkyls, nitroalkyls, carboxyalkyls,hydroxyalkyls, sulfoalkyls, etc. On the other hand, the phrase “alkylmoiety” is limited to the inclusion of only pure open chain saturatedhydrocarbon alkyl substituents, such as methyl, ethyl, propyl, t-butyl,and the like.

[0041] For certain embodiments of R, R¹, R², and A, the organic groupscan include up to 20 carbon atoms (preferably, up to 18 carbon atoms,and more preferably up to 12 carbon atoms).

[0042] For certain embodiments of R, R¹, and R², the organic group caninclude a polymerizable group. Examples of such polymerizable groupsinclude, for example, (meth)acrylamido groups, (meth)acryloxy groups,and vinyl groups. Preferably, the polymerizable groups are(meth)acrylamido groups.

[0043] For certain embodiments of R², the alkyl and alkoxy groups have1-18 carbon atoms (preferably, 1-8 carbon atoms, and more preferably 14carbon atoms), and the aryl and aryloxy groups have 4-18 carbon atoms(preferably, 5-12 carbon atoms, and more preferably 6-10 carbon atoms).For certain embodiments of the present invention, R² is H, OH,(C1-C4)alkyl group, or a (C₁-C₄)alkoxy group. For certain embodiments,R² is OH or a (C1-C4)alkoxy group. For certain embodiments, R² is H, OH,methyl, or methoxy.

[0044] For certain embodiments of R⁴, the alkyl group has 1-18 carbonatoms (preferably, 1-8 carbon atoms, and more preferably 1-4 carbonatoms). For certain embodiments of the present invention, R⁴ is H, a(C1-C4)alkyl group, or can be joined to A forming a cyclic organicgroup. For more preferred embodiments, R⁴ is H or methyl.

[0045] For certain embodiments of the present invention, A is a straightchain alkyl group, preferably having up to 20 carbon atoms. For morepreferred embodiments, A is (CH₂)_(n) wherein n=1-20. For even morepreferred embodiments, A is (CH₂)_(n) wherein n=3-11. For even morepreferred embodiments, n=5.

[0046] Polymerizable Components

[0047] The compositions of the present invention, especiallyself-etching primer and self-etching adhesive compositions, can alsoinclude one or more polymerizable components in addition to thepolymerizable bisphosphonic acid, thereby forming polymerizablecompositions.

[0048] In certain embodiments, the compositions are photopolymerizable,i.e., the compositions contain a photopolymerizable component and aphotoinitiator (i.e., a photoinitiator system) that upon irradiationwith actinic radiation initiates the polymerization (or hardening) ofthe composition. Such photopolymerizable compositions can be freeradically polymerizable.

[0049] In certain embodiments, the compositions are chemicallypolymerizable, i.e., the compositions contain a chemically polymerizablecomponent and a chemical initiator (i.e., initiator system) that canpolymerize, cure, or otherwise harden the composition without dependenceon irradiation with actinic radiation. Such chemically polymerizablecompositions are sometimes referred to as “self-cure” compositions andmay include glass ionomer cements, resin-modified glass ionomer cements,redox cure systems, and combinations thereof.

[0050] Photopolymerizable Compositions

[0051] Suitable photopolymerizable compositions may includephotopolymerizable components (e.g., compounds) that includeethylenically unsaturated compounds (which contain free radically activeunsaturated groups). Examples of useful ethylenically unsaturatedcompounds include acrylic acid esters, methacrylic acid esters,hydroxy-functional acrylic acid esters, hydroxy-functional methacrylicacid esters, and combinations thereof.

[0052] Photopolymerizable compositions may include compounds having freeradically active functional groups that may include monomers, oligomers,and polymers having one or more ethylenically unsaturated groups.Suitable compounds contain at least one ethylenically unsaturated bondand are capable of undergoing addition polymerization. Such freeradically polymerizable compounds include mono-, di- orpoly-(meth)acrylates (i.e., acrylates and methacrylates) such as, methyl(meth)acrylate, ethyl (meth)acrylate, isopropyl (meth)acrylate, n-hexyl(meth)acrylate, stearyl (meth)acrylate, allyl (meth)acrylate, glyceroltri(meth)acrylate, ethyleneglycol di(meth)acrylate, diethyleneglycoldi(meth)acrylate, triethyleneglycol di(meth)acrylate, 1,3-propanedioldi(meth)acrylate, trimethylolpropane tri(meth)acrylate,1,2,4-butanetriol tri(meth)acrylate, 1,4-cyclohexanedioldi(meth)acrylate, pentaerythritol tetra(meth)acrylate, sorbitolhex(meth)acrylate, tetrahydrofurfuryl (meth)acrylate,bis[1-(2-acryloxy)]-p-ethoxyphenyldimethylmethane,bis[1-(3-acryloxy-2-hydroxy)]-p-propoxyphenyldimethylmethane,ethoxylated bisphenolA di(meth)acrylate, andtrishydroxyethyl-isocyanurate tri(meth)acrylate; (meth)acrylamides(i.e., acrylamides and methacrylamides) such as (meth)acrylamide,methylene bis-(meth)acrylamide, and diacetone (meth)acrylamide; urethane(meth)acrylates; the bis-(meth)acrylates of polyethylene glycols(preferably of molecular weight 200-500), copolymerizable mixtures ofacrylated monomers such as those in U.S. Pat. No. 4,652,274 (Boettcheret al.), and acrylated oligomers such as those of U.S. Pat. No.4,642,126 (Zador et al.); and vinyl compounds such as styrene, diallylphthalate, divinyl succinate, divinyl adipate and divinyl phthalate.Other suitable free radically polymerizable compounds includesiloxane-functional (meth)acrylates as disclosed, for example, inWO-00/38619 (Guggenberger et al.), WO-01/92271 (Weinmann et al.),WO-01/07444 (Guggenberger et al.), WO-00/42092 (Guggenberger et al.) andfluoropolymer-functional (meth)acrylates as disclosed, for example, inU.S. Pat. No. 5,076,844 (Fock et al.), U.S. Pat. No. 4,356,296 (Griffithet al.), EP-0373 384 (Wagenknecht et al.), EP-0201 031 (Reiners et al.),and EP-0201 778 (Reiners et al.). Mixtures of two or more free radicallypolymerizable compounds can be used if desired.

[0053] The polymerizable component may also contain hydroxyl groups andfree radically active functional groups in a single molecule. Examplesof such materials include hydroxyalkyl (meth)acrylates, such as2-hydroxyethyl (meth)acrylate and 2-hydroxypropyl (meth)acrylate;glycerol mono- or di-(meth)acrylate; trimethylolpropane mono- ordi-(meth)acrylate; pentaerythritol mono-, di-, and tri-(meth)acrylate;sorbitol mono-, di-, tri-, tetra-, or penta-(meth)acrylate; and2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy)phenyl]propane (bisGMA).Suitable ethylenically unsaturated compounds are also available from awide variety of commercial sources, such as Sigma-Aldrich, St. Louis,Mo. and Rhom and Tech, Inc., Darmstadt, Germany. Mixtures ofethylenically unsaturated compounds can be used if desired.

[0054] The polymerizable component may also be an ethylenicallyunsaturated compound with acid functionality. As used herein,ethylenically unsaturated compounds with acid functionality is meant toinclude monomers, oligomers, and polymers having ethylenic unsaturationand acid and/or acid-precursor functionality. Acid-precursorfunctionalities include, for example, anhydrides, acid halides, andpyrophosphates. Such ethylenically unsaturated compounds with acidfunctionality are present in certain embodiments of the presentinvention.

[0055] Exemplary ethylenically unsaturated compounds with acidfunctionality include, for example, α,β-unsaturated acidic compoundssuch as glycerol phosphate mono(meth)acrylates, glycerol phosphatedi(meth)acrylates, hydroxyethyl (meth)acrylate phosphates, citric acidmono-, di-, and tri-(meth)acrylates, poly(meth)acrylated oligomaleicacid, poly(meth)acrylated polymaleic acid, poly(meth)acrylatedpoly(meth)acrylic acid, poly(meth)acrylated polycarboxyl-polyphosphonicacid, poly(meth)acrylated polychlorophosphoric acid, poly(meth)acrylatedpolysulfonate, poly(meth)acrylated polyboric acid, and the like.Suitable compositions of the present invention include an ethylenicallyunsaturated compound with acid functionality having at least one P—OHmoiety.

[0056] Certain of these compounds are obtained, for example, as reactionproducts between isocyanatoalkyl (meth)acrylates and carboxylic acids(e.g., the bis-isocyanatoethylmethacrylate derivative ofbis-hydroxymethylpropionic acid (PDMA) or thebis-isocyanatoethylmethacrylate derivative of citric acid (CDMA)).Additional compounds of this type having both acid-functional andethylenically unsaturated components are described in U.S. Pat. No.4,872,936 (Engelbrecht) and U.S. Pat. No. 5,130,347 (Mitra). A widevariety of such compounds containing both the ethylenically unsaturatedand acid moieties can be used. Mixtures of such compounds can be used ifdesired.

[0057] Additional ethylenically unsaturated compounds with acidfunctionality include, for example, AA:ITA:IEM (copolymer of acrylicacid:itaconic acid with pendent methacrylate made by reacting AA:ITAcopolymer with sufficient 2-isocyanatoethyl methacrylate to convert aportion of the acid groups of the copolymer to pendent methacrylategroups as described, for example, in Example 11 of U.S. Pat. No.5,130,347 (Mitra)); and those recited in U.S. Pat. No. 4,259,075(Yamauchi et al.), U.S. Pat. No. 4,499,251 (Omura et al.), U.S. Pat. No.4,537,940 (Omura et al.), U.S. Pat. No. 4,539,382 (Omura et al.), U.S.Pat. No. 5,530,038 (Yamamoto et al.), U.S. Pat. No. 6,458,868 (Okada etal.), and European Pat. Application Publication Nos. EP 712,622(Tokuyama Corp.) and EP 1,051,961 (Kuraray Co., Ltd.). Further, thecombination of an ethylenically unsaturated phosphorylated compound anda carboxylic acid functional polymer are disclosed, for example, in U.S.Pat. No. 5,256,447 (Oxman et al.).

[0058] Preferred photopolymerizable components include 2-hydroxyethylmethacrylate (HEMA), PEGDMA (polyethyleneglycol dimethacrylate having amolecular weight of about 400), AA:ITA:IEM (copolymer of acrylicacid:itaconic acid with pendent methacrylate as described in theExamples Section), bisGMA, UDMA (urethane dimethacrylate), and GDMA(glycerol dimethacrylate).

[0059] Various combinations of the polymerizable components can be usedif desired.

[0060] Suitable photoinitiators (i.e., photoinitiator systems thatinclude one or more compounds) for polymerizing free radicallyphotopolymerizable compositions include binary and tertiary systems.Typical binary photoinitiators include a photosensitizer and an electrondonor compound. Typical tertiary photoinitiators include an iodoniumsalt, a photosensitizer, and an electron donor compound as described inU.S. Pat. No. 5,545,676 (Palazzotto et al.). Preferred iodonium saltsare the diaryl iodonium salts, e.g., diphenyliodonium chloride,diphenyliodonium hexafluorophosphate, and diphenyliodoniumtetrafluoroboarate. Preferred photosensitizers are monoketones anddiketones that absorb some light within a range of about 450 nm to about520 nm (preferably, about 450 nm to about 500 nm).

[0061] Exemplary alpha-diketones include 2,3-butanedione,2,3-pentanedione, 2,3-hexanedione, 3,4-hexanedione, 2,3-heptanedione,3,4-heptanedione, 2,3-octanedione, 4,5-octanedione, benzil, 2,2′-,3,3′-, and 4,4′-dihydroxybenzil, furil, di-3,3′-indolylethanedione,2,3-bomanedione (camphorquinone), biacetyl, 1,2-cyclohexanedione,3,3,6,6-tetramethylcyclohexanedione, 1,2-naphthaquinone,acenaphthaquinone, and the like. Additional diketones include1-aryl-2-alkyl-1,2-ethanediones such as 1-phenyl-1,2-propanedione, asdisclosed, for example, in U.S. Pat. No. 6,204,302 (Rawls et al.). Morepreferred compounds are alpha diketones that have some light absorptionwithin a range of about 450 nm to about 520 nm (even more preferably,about 450 to about 500 nm). Preferred compounds are camphorquinone,benzil, furil, 3,3,6,6-tetramethylcyclohexanedione, phenanthraquinoneand other cyclic alpha diketones. Most preferred is camphorquinone.

[0062] Preferred electron donor compounds include substituted amines,e.g., ethyl dimethylaminobenzoate.

[0063] Other suitable photoinitiators for polymerizing free radicallyphotopolymerizable compositions include the class of phosphine oxidesthat typically have a functional wavelength range of about 380 nm toabout 1200 nm. Preferred phosphine oxide free radical initiators with afunctional wavelength range of about 380 nm to about 450 nm are acyl andbisacyl phosphine oxides such as those described in U.S. Pat. No.4,298,738 (Lechtken et al.), U.S. Pat. No. 4,324,744 (Lechtken et al.),U.S. Pat. No. 4,385,109 (Lechtken et al.), U.S. Pat. No. 4,710,523(Lechtken et al.), and U.S. Pat. No. 4,737,593 (Ellrich et al.), U.S.Pat. No. 6,251,963 (Kohler et al.); and EP Application No. 0 173 567 A2(Ying).

[0064] Commercially available phosphine oxide photoinitiators capable offree-radical initiation when irradiated at wavelength ranges of greaterthan about 380 nm to about 450 nm includebis(2,4,6-trimethylbenzoyl)phenyl phosphine oxide (IRGACURE 819, CibaSpecialty Chemicals, Tarrytown, N.Y.),bis(2,6-dimethoxybenzoyl)-(2,4,4-trimethylpentyl) phosphine oxide (CGI403, Ciba Specialty Chemicals), a 25:75 mixture, by weight, ofbis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentyl phosphine oxide and2-hydroxy-2-methyl-1-phenylpropan-1-one (IRGACURE 1700, Ciba SpecialtyChemicals), a 1:1 mixture, by weight, ofbis(2,4,6-trimethylbenzoyl)phenyl phosphine oxide and2-hydroxy-2-methyl-1-phenylpropane-1-one (DAROCUR 4265, Ciba SpecialtyChemicals), and ethyl 2,4,6-trimethylbenzylphenyl phosphinate (LUCIRINLR8893X, BASF Corp., Charlotte, N.C.).

[0065] Typically, the phosphine oxide initiator is present in thephotopolymerizable composition in catalytically effective amounts, suchas from about 0.1 weight percent to about 5.0 weight percent, based onthe total weight of the composition.

[0066] Tertiary amine reducing agents may be used in combination with anacylphosphine oxide. Illustrative tertiary amines useful in theinvention include ethyl 4-(N,N-dimethylamino)benzoate andN,N-dimethylaminoethyl methacrylate. When present, the amine reducingagent is present in the photopolymerizable composition in an amount fromabout 0.1 weight percent to about 5.0 weight percent, based on the totalweight of the composition.

[0067] Chemically Polymerizable Compositions

[0068] The chemically polymerizable compositions may include glassionomer cements such as conventional glass ionomers that typicallyemploy as their main ingredients a homopolymer or copolymer of anethylenically unsaturated carboxylic acid (e.g., poly(acrylic acid),copoly(acrylic, itaconic acid), copoly(acrylic, maleic acid), and thelike), a fluoroaluminosilicate (“FAS”) glass, water, and a chelatingagent such as tartaric acid. Conventional glass ionomers (i.e., glassionomer cements) typically are supplied in powder/liquid formulationsthat are mixed just before use. The mixture will undergo self-hardeningin the dark due to an ionic reaction between the acidic repeating unitsof the polycarboxylic acid and cations leached from the glass.

[0069] The glass ionomer cements may include resin-modified glassionomer (“RMGI”) cements. Like a conventional glass ionomer, an RMGIcement employs an FAS glass. However, the organic portion of an RMGI isdifferent. In one type of RMGI, the polycarboxylic acid is modified toreplace or end-cap some of the acidic repeating units with pendentcurable groups and a photoinitiator is added to provide a second curemechanism, e.g., as described in U.S. Pat. No. 5,130,347 (Mitra).Acrylate or methacrylate groups are usually employed as the pendantcurable group. In another type of RMGI, the cement includes apolycarboxylic acid, an acrylate or methacrylate-functional monomer anda photoinitiator, e.g., as in Mathis et al., “Properties of a New Glasslonomer/Composite Resin Hybrid Restorative,” Abstract No. 51, J. DentRes., 66:113 (1987) and as in U.S. Pat. No. 5,063,257 (Akahane et al.),U.S. Pat. No. 5,520,725 (Kato et al.), U.S. Pat. No. 5,859,089 (Qian),U.S. Pat. No. 5,925,715 (Mitra) and U.S. Pat. No. 5,962,550 (Akahane etal.). In another type of RMGI, the cement may include a polycarboxylicacid, an acrylate or methacrylate-functional monomer, and a redox orother chemical cure system, e.g., as described in U.S. Pat. No.5,154,762 (Mitra et al.), U.S. Pat. No. 5,520,725 (Kato et al.), andU.S. Pat. No. 5,871,360 (Kato). In another type of RMGI, the cement mayinclude various monomer-containing or resin-containing components asdescribed in U.S. Pat. No. 4,872,936 (Engelbrecht), U.S. Pat. No.5,227,413 (Mitra), U.S. Pat. No. 5,367,002 (Huang et al.), and U.S. Pat.No. 5,965,632 (Orlowski). RMGI cements are preferably formulated aspowder/liquid or paste/paste systems, and contain water as mixed andapplied. The compositions are able to harden in the dark due to theionic reaction between the acidic repeating units of the polycarboxylicacid and cations leached from the glass, and commercial RMGI productstypically also cure on exposure of the cement to light from a dentalcuring lamp. RMGI cements that contain a redox cure system and that canbe cured in the dark without the use of actinic radiation are describedin U.S. Patent Publication No. 2003/0087986 (Filed Jul. 27, 2001).

[0070] The chemically polymerizable compositions may include redox curesystems that include a polymerizable component (e.g., an ethylenicallyunsaturated polymerizable component) and redox agents that include anoxidizing agent and a reducing agent. Suitable polymerizable components,redox agents, optional acid-functional components, and optional fillersthat are useful in the present invention are described in U.S. PatentPublication No. 2003/0166740 (Filed Apr. 12, 2002) and U.S. PatentPublication No. 2003/0195273 (Filed Apr. 12, 2002).

[0071] The reducing and oxidizing agents should react with or otherwisecooperate with one another to produce free-radicals capable ofinitiating polymerization of the resin system (e.g., the ethylenicallyunsaturated component). This type of cure is a dark reaction, that is,it is not dependent on the presence of light and can proceed in theabsence of light. The reducing and oxidizing agents are preferablysufficiently shelf-stable and free of undesirable colorization to permittheir storage and use under typical dental conditions. They should besufficiently miscible with the resin system (and preferablywater-soluble) to permit ready dissolution in (and discourage separationfrom) the other components of the polymerizable composition.

[0072] Useful reducing agents include ascorbic acid, ascorbic acidderivatives, and metal complexed ascorbic acid compounds as described inU.S. Pat. No. 5,501,727 (Wang et al.); amines, especially tertiaryamines, such as 4-tert-butyl dimethylaniline; aromatic sulfinic salts,such as p-toluenesulfinic salts and benzenesulfinic salts; thioureas,such as 1-ethyl-2-thiourea, tetraethyl thiourea, tetramethyl thiourea,1,1-dibutyl thiourea, and 1,3-dibutyl thiourea; and mixtures thereof.Other secondary reducing agents may include cobalt (II) chloride,ferrous chloride, ferrous sulfate, hydrazine, hydroxylamine (dependingon the choice of oxidizing agent), salts of a dithionite or sulfiteanion, and mixtures thereof. Preferably, the reducing agent is an amine.

[0073] Suitable oxidizing agents will also be familiar to those skilledin the art, and include but are not limited to persulfuric acid andsalts thereof, such as sodium, potassium, ammonium, cesium, and alkylammonium salts. Additional oxidizing agents include peroxides such asbenzoyl peroxides, hydroperoxides such as cumyl hydroperoxide, t-butylhydroperoxide, and amyl hydroperoxide, as well as salts of transitionmetals such as cobalt (III) chloride and ferric chloride, cerium (IV)sulfate, perboric acid and salts thereof, permanganic acid and saltsthereof, perphosphoric acid and salts thereof, and mixtures thereof.

[0074] It may be desirable to use more than one oxidizing agent or morethan one reducing agent. Small quantities of transition metal compoundsmay also be added to accelerate the rate of redox cure. In someembodiments it may be preferred to include a secondary ionic salt toenhance the stability of the polymerizable composition as described inU.S. Patent Publication No. 2003/0195273 (Filed Apr. 12, 2002).

[0075] The reducing and oxidizing agents are present in amountssufficient to permit an adequate free-radical reaction rate. This can beevaluated by combining all of the ingredients of the polymerizablecomposition except for the optional filler, and observing whether or nota hardened mass is obtained.

[0076] Preferably, a reducing agent is present in an amount of at leastabout 0.01 wt-%, and more preferably at least about 0.1 wt-%, based onthe total weight (including water) of the components of thepolymerizable composition. Preferably, a reducing agent is present in anamount of no greater than about 10 wt-%, and more preferably no greaterthan about 5 wt-%, based on the total weight (including water) of thecomponents of the polymerizable composition.

[0077] Preferably, an oxidizing agent is present in an amount of atleast about 0.01 wt-%, and more preferably at least about 0.10 wt-%,based on the total weight (including water) of the components of thepolymerizable composition. Preferably, an oxidizing agent is present inan amount of no greater than about 10 wt-%, and more preferably nogreater than about 5 wt-%, based on the total weight (including water)of the components of the polymerizable composition.

[0078] The reducing or oxidizing agents can be microencapsulated asdescribed in U.S. Pat. No. 5,154,762 (Mitra et al.). This will generallyenhance shelf stability of the polymerizable composition, and ifnecessary permit packaging the reducing and oxidizing agents together.For example, through appropriate selection of an encapsulant, theoxidizing and reducing agents can be combined with an acid-functionalcomponent and optional filler and kept in a storage-stable state.Likewise, through appropriate selection of a water-insolubleencapsulant, the reducing and oxidizing agents can be combined with anFAS glass and water and maintained in a storage-stable state.

[0079] A redox cure system can be combined with other cure systems,e.g., with a glass ionomer cement and with a photopolymerizablecomposition such as described U.S. Pat. No. 5,154,762 (Mitra et al.).

[0080] The polymerizable compositions that utilize a redox cure systemcan be supplied in a variety of forms including two-part powder/liquid,paste/liquid, and paste/paste systems. Other forms employing multi-partcombinations (i.e., combinations of two or more parts), each of which isin the form of a powder, liquid, gel, or paste are also possible. In amulti-part system, one part typically contains the reducing agent(s) andanother part typically contains the oxidizing agent(s). Therefore, ifthe reducing agent is present in one part of the system, then theoxidizing agent is typically present in another part of the system.However, the reducing agent and oxidizing agent can be combined in thesame part of the system through the use of the microencapsulationtechnique.

[0081] Optional Fillers

[0082] The compositions of the present invention can also containfillers. Fillers may be selected from one or more of a wide variety ofmaterials suitable for incorporation in compositions used for dentalapplications, such as fillers currently used in dental restorativecompositions, and the like.

[0083] The filler is preferably finely divided. The filler can have aunimodial or polymodial (e.g., bimodal) particle size distribution.Preferably, the maximum particle size (the largest dimension of aparticle, typically, the diameter) of the filler is less than about 10micrometers, and more preferably less than about 2.0 micrometers.Preferably, the average particle size of the filler is less than about3.0 micrometers, and more preferably less than about 0.6 micrometer.

[0084] The filler can be an inorganic material. It can also be acrosslinked organic material that is insoluble in the resin system, andis optionally filled with inorganic filler. The filler should in anyevent be nontoxic and suitable for use in the mouth. The filler can beradiopaque or radiolucent. The filler typically is substantiallyinsoluble in water.

[0085] Examples of suitable inorganic fillers are naturally occurring orsynthetic materials including, but not limited to: quartz; nitrides(e.g., silicon nitride); glasses derived from, for example, Ce, Sb, Sn,Ba, Zn, and Al; feldspar; borosilicate glass; kaolin; talc; titania; lowMohs hardness fillers such as those described in U.S. Pat. No. 4,695,251(Randklev); and submicron silica particles (e.g., pyrogenic silicas suchas those available under the trade designations AEROSIL, including “OX50,” “130,” “150” and “200” silicas from Degussa Corp., Akron, Ohio andCAB-O-SIL M5 silica from Cabot Corp., Tuscola, Ill.). Examples ofsuitable organic filler particles include filled or unfilled pulverizedpolycarbonates, polyepoxides, and the like.

[0086] Preferred non-acid-reactive filler particles are quartz,submicron silica, and non-vitreous microparticles of the type describedin U.S. Pat. No. 4,503,169 (Randklev). Mixtures of thesenon-acid-reactive fillers are also contemplated, as well as combinationfillers made from organic and inorganic materials.

[0087] The surface of the filler particles can also be treated with acoupling agent in order to enhance the bond between the filler and theresin. The use of suitable coupling agents includegamma-methacryloxypropyltrimethoxysilane,gamma-mercaptopropyltriethoxysilane, gamma-aminopropyltrimethoxysilane,and the like.

[0088] The filler can also be an acid-reactive filler. An acid-reactivefiller is typically used in combination with an acid-functional resincomponent, and may or may not be used in combination with a nonreactivefiller. The acid-reactive filler can, if desired, also possess theproperty of releasing fluoride. Suitable acid-reactive fillers includemetal oxides, glasses, and metal salts. Preferred metal oxides includebarium oxide, calcium oxide, magnesium oxide, and zinc oxide. Preferredglasses include borate glasses, phosphate glasses, andfluoroaluminosilicate (“FAS”) glasses. FAS glasses are particularlypreferred. The FAS glass preferably contains sufficient elutable cationsso that a hardened dental composition will form when the glass is mixedwith the components of the hardenable composition. The glass alsopreferably contains sufficient elutable fluoride ions so that thehardened composition will have cariostatic properties. The glass can bemade from a melt containing fluoride, alumina, and other glass-formingingredients using techniques familiar to those skilled in the FASglassmaking art. The FAS glass preferably is in the form of particlesthat are sufficiently finely divided so that they can conveniently bemixed with the other cement components and will perform well when theresulting mixture is used in the mouth.

[0089] Preferably, the average particle size (typically, diameter) forthe FAS glass is no greater than about 10 micrometers, and morepreferably no greater than about 5 micrometers as measured using, forexample, a sedimentation analyzer. Suitable FAS glasses will be familiarto those skilled in the art, and are available from a wide variety ofcommercial sources, and many are found in currently available glassionomer cements such as those commercially available under the tradedesignations VITREMER, VITREBOND, RELY X LUTING CEMENT and KETAC-FIL (3MESPE Dental Products, St. Paul, Minn.), FUJI II, GC FUJI LC and FUJI IX(G-C Dental Industrial Corp., Tokyo, Japan) and CHEMFIL Superior(Dentsply International, York, Pa.). Mixtures of fillers can be used ifdesired.

[0090] The FAS glass can optionally be subjected to a surface treatment.Suitable surface treatments include, but are not limited to, acidwashing (e.g., treatment with a phosphoric acid), treatment with aphosphate, treatment with a chelating agent such as tartaric acid, andtreatment with a silane or an acidic or basic silanol solution.Desirably the pH of the treating solution or the treated glass isadjusted to neutral or near-neutral, as this can increase storagestability of the hardenable composition.

[0091] In certain compositions mixtures of acid-reactive andnon-acid-reactive fillers can be used either in the same part or indifferent parts.

[0092] Other suitable fillers are disclosed in U.S. Pat. No. 6,387,981(Zhang et al.) as well as International Publication Nos. WO 01/30304 (Wuet al.), WO 01/30305 (Zhang et al.), WO 01/30306 (Windisch et al.), andWO 01/30307 (Zhang et al.).

[0093] U.S. Pat. No. 6,306,926 (Bretscher et al.) discloses a number ofradiopacifying fillers that can be used in both free radicallypolymerizable compositions, cationically polymerizable compositions, andhybrid compositions featuring both free radically and cationicallypolymerizable components. They are particularly advantageous for use incationically polymerizable compositions. One such filler is amelt-derived filler that includes 5-25% by weight aluminum oxide, 10-35%by weight boron oxide, 15-50% by weight lanthanum oxide, and 20-50% byweight silicon oxide. Another filler is a melt-derived filler thatincludes 10-30% by weight aluminum oxide, 10-40% by weight boron oxide,20-50% by weight silicon oxide, and 15-40% by weight tantalum oxide. Athird filler is a melt-derived filler that includes 5-30% by weightaluminum oxide, 5-40% by weight boron oxide, 0-15% by weight lanthanumoxide, 25-55% by weight silicon oxide, and 1040% by weight zinc oxide. Afourth filler is a melt-derived filler that includes 15-30% by weightaluminum oxide, 15-30% by weight boron oxide, 20-50% by weight siliconoxide, and 15-40% by weight ytterbium oxide. A fifth filler is in theform of non-vitreous microparticles prepared by a sol-gel method inwhich an aqueous or organic dispersion or sol of amorphous silicon oxideis mixed with an aqueous or organic dispersion, sol, or solution of aradiopacifying metal oxide, or precursor organic or compound. A sixthfiller is in the form of non-vitreous microparticles prepared by asol-gel method in which an aqueous or organic dispersion or sol ofamorphous silicon oxide is mixed with an aqueous or organic dispersion,sol, or solution of a radiopacifying metal oxide, or precursor organicor inorganic compound.

[0094] Optional Photobleachable Dye

[0095] In some embodiments, compositions of the present inventionpreferably have an initial color remarkably different than dentalstructures. Color is preferably imparted to a composition through theuse of a photobleachable dye. A composition of the present inventionpreferably includes at least 0.001% by weight photobleachable dye, andmore preferably at least 0.002% by weight photobleachable dye, based onthe total weight of the composition. A composition of the presentinvention preferably includes at most 1% by weight photobleachable dye,and more preferably at most 0.1% by weight photobleachable dye, based onthe total weight of the composition. The amount of photobleachable dyemay vary depending on its extinction coefficient, the ability of thehuman eye to discern the initial color, and the desired color change.

[0096] The color formation and bleaching characteristics of thephotobleachable dye varies depending on a variety of factors including,for example, acid strength, dielectric constant, polarity, amount ofoxygen, and moisture content in the atmosphere. However, the bleachingproperties of the dye can be readily determined by irradiating thecomposition and evaluating the change in color. Preferably, at least onephotobleachable dye is at least partially soluble in a hardenable resin.

[0097] Exemplary classes of photobleachable dyes are disclosed, forexample, in U.S. Pat. No. 6,331,080 (Cole et al.), U.S. Pat. No.6,444,725 (Trom et al.), and U.S. Pat. No. 6,528,555 (Nikutowski etal.). Preferred dyes include, for example, Rose Bengal, MethyleneViolet, Methylene Blue, Fluorescein, Eosin Yellow, Eosin Y, Ethyl Eosin,Eosin bluish, Eosin B, Erythrosin B, Erythrosin Yellowish Blend,Toluidine Blue, 4′,5′-Dibromofluorescein, and combinations thereof.

[0098] The color change in the inventive compositions is initiated bylight. Preferably, the composition's color change is initiated usingactinic radiation using, for example, a dental curing light which emitsvisible or near infrared (1R) light for a sufficient amount of time. Themechanism that initiates the color change in the compositions of theinvention may be separate from or substantially simultaneous with thehardening mechanism that hardens the resin. For example, a compositionmay harden when polymerization is initiated chemically (e.g., redoxinitiation) or thermally, and the color change from an initial color toa final color may occur subsequent to the hardening process uponexposure to actinic radiation.

[0099] The change in composition color from an initial color to a finalcolor is preferably quantified by a Color Test as described below. Usingthe Color Test, a value of ΔE* is determined, which indicates the totalcolor change in a 3-dimensional color space. The human eye can detect acolor change of approximately 3 ΔE* units in normal lighting conditions.The dental compositions of the present invention are preferably capableof having a color change, ΔE*, of at least 20; more preferably, ΔE* isat least 30; most preferably ΔE* is at least 40.

[0100] Optional Additives

[0101] Optionally, the polymerizable compositions also may containsolvents or diluents (e.g., water, alcohols (e.g., propanol, ethanol),ketones (e.g., acetone, methyl ethyl ketone), and other nonaqueoussolvents (e.g., dimethylformamide, dimethylacetamide, dimethylsulfoxide,1-methyl-2-pyrrolidinone)). If desired, the compositions of theinvention can contain additives such as pigments, inhibitors,accelerators, viscosity modifiers, surfactants, fluoride releasingagents, and other ingredients that will be apparent to those skilled inthe art.

[0102] Suitable fluoride releasing agents include fluoride salts asdisclosed, for example, in U.S. Pat. No. 5,607,663 (Rozzi et al.), U.S.Pat. No. 5,662,887 (Rozzi et al.), U.S. Pat. No. 5,866,630 (Mitra etal.), U.S. Pat. No. 5,876,208 (Mitra et al.), U.S. Pat. No. 5,888,491(Mitra et al.), and U.S. Pat. No. 6,312,668 (Mitra et al.). A preferredfluoride releasing agent includes tetrafluoroborate anions as disclosed,for example, in U.S. Pat. No. 4,871,786 (Aasen et al.). A preferredrepeating unit of a fluoride releasing agent includestrimethylammoniumethyl methacrylate.

[0103] Dental Primers

[0104] Numerous examples of hard tissue dental primers are known, whichcan be used as a component of compositions of the present invention oras a separate primer used in conjunction with compositions of thepresent invention. For example, U.S. Pat. No. 5,554,030 (Ario et al.)and U.S. Pat. No. 5,525,648 (Aasen et al.) include a variety ofmaterials and methods for applying a priming solution containing afilm-former to an etched dental surface. Such materials and methods aredescribed as part of an overall sequence of method steps for bondingdental restorative materials to a dental surface. Examples ofcommercially available dental primers include SCOTCHBOND MULTI-PURPOSEPrimer available from 3M ESPE Dental, St. Paul, Minn. and CLEARFIL SE(self-etching primer) available from Kuraray Company, Japan.

[0105] Dental Adhesives

[0106] Numerous examples of hard tissue adhesives are known, which canbe used as a component of compositions of the present invention or as aseparate adhesive used in conjunction with compositions of the presentinvention. For example, U.S. Pat. No. 4,719,149 (Aasen et al.) andreferences therein include a variety of materials and methods foradhering methacrylate-based composites to hard tissues. There are manyother patents that describe various preferred materials and protocolsfor bonding to teeth, such as for example, U.S. Pat. No. 5,256,447(Oxman et al.) and U.S. Pat. No. 5,525,648 (Aasen et al.). U.S. Pat. No.5,980,253 (Oxman et al.) describes materials and methods for bondingcationically curable compositions to hard tissues.

[0107] Such known materials and methods can be used in the processes ofthe present invention. Generally, these materials have been used inprocesses that initially harden the adhesive and then the restorativematerial. That is, conventional methods utilize one or more of thefollowing steps: surface treatment of the tooth (e.g., etching,priming), application of a hardenable adhesive to the primed toothsurface, curing of the adhesive, placement of a restorative material onthe hardened adhesive, and curing of the restorative material. Examplesof commercially available dental adhesives and adhesive systems includeSCOTCHBOND MULTI-PURPOSE adhesive, SINGLEBOND adhesive (self-primingadhesive), and ADPER PROMPT L-POP (self-etching adhesive) all availablefrom 3M ESPE Dental, St. Paul, Minn.

[0108] Methods and Kits

[0109] A composition of the present invention is applied to a hardsurface, typically a dental structure requiring restoration, for a timesufficient to etch, and preferably etch and prime, the surface, usingconventional techniques. Thereafter, optionally, the applied compositionmay be rinsed, dried, or both. More preferably, a composition of thepresent invention is a self-etching adhesive that requires only a singleapplication. Specific techniques are described in greater detail in theExamples Section.

[0110] Certain methods of the present invention involve adhering anorthodontic appliance (e.g., a bracket, a buccal tube, a band, a cleat,a button, a lingual retainer, and a bite blocker) to the tooth surfaceafter the tooth surface has been etched by a composition including apolymerizable bisphosphonic acid. In such embodiments, an orthodonticadhesive can be adhered to the tooth surface, which can optionally bepre-applied to the orthodontic appliance before adhering to the toothsurface.

[0111] In the case of utilizing an orthodontic adhesive to adhere anorthodontic appliance to a tooth surface, the following steps havetraditionally been used to prepare the tooth surface: etchantapplication (typically a phosphoric acid solution), rinse, dry, primerapplication, dry, orthodontic adhesive application. By using an etchingcomposition of the present invention (containing a polymerizablebisphosphonic acid compound of the present invention), it should bepossible to eliminate, at a minimum, the rinsing step of the traditionalprocess; and additionally eliminate the bitter aftertaste that patientsexperience from the use of phosphoric acid. By using self-etching primeror self-etching adhesive compositions of the present invention,additional steps of the traditional process can be eliminated aspreviously discussed herein.

[0112] For example, if the composition further includes at least onepolymerizable component different from the polymerizable bisphosphonicacid, steps of etching and priming are done simultaneously with thecomposition functioning as a self-etching primer composition.Alternatively, if the composition further includes at least onepolymerizable component different from the polymerizable bisphosphonicacid, steps of etching and applying a dental adhesive are donesimultaneously with the composition acting as a self-etching adhesivecomposition. For certain embodiments, the methods of the presentinvention can include adhering an orthodontic adhesive to the toothsurface, wherein preferably the orthodontic adhesive has beenpre-applied to the orthodontic appliance before adhering to the toothsurface.

[0113] For embodiments in which the composition functions only as aself-etching primer, an adhesive is subsequently applied to the primedhard surface. Typically, the adhesive contains an initiator and eitherimmediately before or immediately after application of the adhesive,curing is initiated to form a polymeric structure on the hard surface.

[0114] The components of the compositions can be used in kit form withvarious containers. For example, an etchant composition can be packagedalong with separate containers of dental primers and dental adhesives oralong with a separate container of a self-priming adhesive.Alternatively, a self-etching primer composition can be packaged alongwith a separate container of adhesive. As other embodiments, aself-etching adhesive composition could be packaged as a two-part systemrequiring mixing immediately prior to application and/or could bepackaged along with a suitable applicator.

EXAMPLES

[0115] Objects and advantages of this invention are further illustratedby the following examples, but the particular materials and amountsthereof recited in these examples, as well as other conditions anddetails, should not be construed to unduly limit this invention. Unlessotherwise indicated, all parts and percentages are on a weight basis,all water is deionized water, and all molecular weights are weightaverage molecular weight.

Test Methods Shear Bond Strength to Enamel and Dentin Test

[0116] Preparation of Teeth. Bovine incisal teeth, free of soft tissue,were embedded in circular acrylic disks. The embedded teeth were storedin water in a refrigerator prior to use. In preparation for adhesivetesting, the embedded teeth were ground to expose a flat enamel ordentin surface using 120-grit sandpaper mounted on a lapidary wheel.Further grinding and polishing of the tooth surface was done using320-grit sandpaper on the lapidary wheel. The teeth were continuouslyrinsed with water during the grinding process.

[0117] Teeth Treatment. A test sample was applied with a dentalapplicator brush over the entire surface of the prepared enamel ordentin surface and allowed to stand on the tooth surface for about 20seconds. The coating was then thinned using a gentle to moderate streamof air for about 1-2 seconds. Using a clean application brush, anovercoat adhesive layer was optionally applied on top of the samplelayer. The adhesive materials utilized are shown in Table 1. Theovercoat adhesive layer was air thinned with a gentle stream of air forabout 1-2 seconds and then light cured for 10 seconds. A 2.5-mm thickTeflon mold with a hole approximately 4.7 mm in diameter was clamped tothe embedded tooth such that the hole in the mold exposed part of theadhesively prepared tooth surface. A composite material, FILTEK Z250Universal Restorative (3M Company, St. Paul, Minn.), was filled into thehole such that the hole was completely filled, but not overfilled, andlight cured per manufacturer's instructions to form a “button” that wasadhesively attached to the tooth.

[0118] Shear Bond Strength Testing. The molds were carefully removedfrom the embedded teeth, leaving the button of FILTEK Z250 compositeattached to each tooth surface. One at a time, the samples were mountedin an INSTRON machine such that the tooth surface was parallel to thedirection of the pulling shear force. A loop of wire (0.75-mm thick) wasplaced around the button flush with the tooth surface, and the pullingshear force was started at a crosshead speed of 2 mm/minute. The forcein kilograms (kg) at which the bond failed was recorded, and this numberwas converted to a force per unit area (units of kg/cm² or MPa) usingthe known surface area of the button. Each reported value represents theaverage of 5 replicates. Abbreviations/Definitions AA:ITA Copolymer madefrom a 4:1 mole ratio of acrylic acid:itaconic acid, prepared accordingto Example 3 of U.S. Pat. No. 5,130,347 (Mitra), MW (average) = 106,000;polydispersity ρ = 4.64. IEM 2-Isocyanoethyl methacrylate(Sigma-Aldrich, St. Louis, MO) AA:ITA:IEM Polymer made by reactingAA:ITA copolymer with sifficient IEM to convert 16 mole percent of theacid groups of the copolymer to pendent methacrylate groups, accordingto the dry polymer preparation of Example 11 of U.S. Pat. No. 5,130,347.HEMA 2-Hydroxyethyl methacrylate (Sigma-Aldrich) CPQ Camphorquinone(Sigma-Aldrich) EDMAB Ethyl 4-(N,N-dimethylamino)benzoate(Sigma-Aldrich) DPIHFP Diphenyliodonium Hexafluorophosphate (Alfa Aesar,Ward Hill, MA) PEGDMA 400 Polyethyleneglycol dimethacrylate (Sartomer,Exton, PA)

Starting Materials

[0119] Compound A (6-Amino-1-hydroxyhexylidene)bisphosphonic AcidMonosodium Salt)

[0120] A 250-ml 3-neck flask was equipped with a mechanical stirrer, dryice/acetone condenser connected to a caustic scrubber, and athermocouple. The system was flushed with nitrogen for 20 minutes. Addedwith continuous stirring at room temperature were 6-aminocaproic acid(52.5 g, 0.40 mol; Sigma-Aldrich), phosphorous acid (32 g, 0.38 mol),and methanesulfonic acid (160 ml). The mixture was heated to 65° C. andthen phosphorus trichloride (PCl₃, 70 ml, 0.80 mol) was added over 20minutes using a dropping funnel. Stirring was continued at 65° C.overnight. The clear reaction mixture was cooled to 30° C. and thenquenched into 400 ml of ice-cold water. An additional 200 ml of waterwas used to rinse the reaction flask and then added to the cold mixture.The aqueous mixture was warmed to room temperature and then heated toreflux for 5 hours. The mixture was cooled to 20° C. and the pH wasraised to 4.3 using 50 wt.-% aqueous sodium hydroxide. The clear mixturewas cooled in an ice bath for 2 hours during which time a whitecrystalline solid formed. The solid was isolated by vacuum filtration.The filter cake was washed with ice-cold water (2 50-ml portions) andthen ethanol (100 ml). The white solid was dried by air for 2 days andthen with a vacuum pump overnight to give a white solid in 93% yield.The solid was characterized as(6-amino-1-hydroxyhexylidene)bisphosphonic acid monosodium salt(Compound A) having the following Nuclear Magnetic Resonance (NMR)values: ¹H NMR (D₂O) ρ 2.90 (t, 2H), 1.84-1.94 (m, 2H), 1.62-1.70 (m,2H), 1.53-1.61 (m, 2H), 1.32-1.40 (m, 2H); ¹³C NMR σ 74.5 (t), 39.5,33.5, 26.5 (s+s), 23; ³¹P NMR σ 19.5.

[0121] Compound B (4-Amino-1-hydroxybutylidene)bisphosphonic AcidMonosodium Salt)

[0122] Compound B was prepared from 4-aminobutyric acid (Sigma-Aldrich)by the same procedure as described for Compound A. A white solid wasisolated in 90.8% yield and was characterized as(4-amino-1-hydroxybutylidene)bisphosphonic acid monosodium salt(Compound B) having the following NMR values: ¹H NMR (D₂O) σ 3.0 (m,2H), 2.0 (m, 4H); ¹³C NMR σ 74.5 (t), 41, 32, 24; ³¹P NMR σ 19.0 (s).

[0123] Compound C (12-Amino-1-hydroxydodecylidene)bisphosphonic Acid)

[0124] A 250-ml flask was fitted with a mechanical stirrer, athermocouple, an addition funnel, and a reflux condenser with dry icewhich was connected to a caustic scrubber. The system was flushed withnitrogen and charged with 12-aminododecanoic acid (21.04 g, 0.098 mol;Advanced Synthesis Technologies, San Ysidro, Calif.), phosphorous acid(8.00 g, 0.098 mol), and methanesulfonic acid (40 ml). The mixture washeated to 65° C., PCl₃ (26.83 g, 0.195 mol) was added over 20 min, andthe mixture was maintained at 65° C. overnight. The mixture was cooledto 60° C. and water (75 ml) was added dropwise over 30 minutes. Themixture was then heated to reflux for 5 hours. After cooling to 30° C.,the flask contents were precipitated with excess water. The solid wasfiltered, washed several times with water, and air-dried for 2 days toafford a white solid (32 g, 82.5%). The solid was characterized as(12-amino-1-hydroxydodecylidene)bisphosphonic acid (Compound C) havingthe following NMR values (recorded using a KOH solution of the solid):¹H NMR (D₂O) σ 2.45 (t, 2H), 1.65-1.80 (m, 2H), 1.35-1.45 (m, 2H),1.25-1.30 (m, 2H), 1.05-1.20 (m, 14H); ¹³C NMR σ 77.1 (t), 40.9, 36.7,32, 30.8, 29.4 (s+s), 29.0, 28.8 (s+s), 26, 24; ³¹P NMR σ19.5 (s).

[0125] Compound D (11-Amino-1-hydroxyundecylidene)bisphosphonic Acid)

[0126] Compound D was prepared from 11-aminoundecanoic acid(Sigma-Aldrich) by the same procedure as described for Compound C. Awhite solid was isolated in 92.96% yield and was determined to have ¹H,13C, and ³¹P NMR values (recorded using a KOH solution of the solid)consistent with the compound(11-amino-1-hydroxyundecylidene)bisphosphonic acid (Compound D).

Example 1 (1-Hydroxy-6-methacrylamidohexylidene)bisphosphonic Acid(Formula II: R³═CH₃, R⁴═H, x=1, R²═OH, and A=(CH₂)₅)

[0127] Sodium hydroxide pellets (46.5 g, 1.16 mol) were dissolved inwater (150 ml) in a 500-ml 2-neck flask equipped with a mechanicalstirrer. The solution was cooled in an ice bath for 15 minutes. Withvigorous stirring, Compound A (50 g, 0.182 mol) was added and theresulting mixture stirred until a clear solution was obtained. To thecold solution was added methacryloyl chloride (21.0 g, 0.200 mol)dropwise over 10 minutes. The mixture was vigorously stirred in the icebath for 3 hours (pH above 9). The mixture was acidified usingconcentrated HCl until pH paper indicated a pH value below 2. Methanol(500 ml) was added and the precipitated solid (NaCl) was removed byvacuum filtration. The filtrate was concentrated in a rotary evaporatorand the obtained residue was dissolved in methanol (200 ml). Theresulting cloudy solution was filtered through a celite bed and theclear filtrate was concentrated in a rotary evaporator to afford a solidthat was dried in a vacuum pump at 40° C. overnight to give a whitesolid quantitatively (i.e., 100% yield). The solid was characterized as(1-hydroxy-6-methacrylamidohexylidene)bisphosphonic acid (Example 1)having the following NMR values: ¹H NMR (D20) σ 5.65 (s, 1H), 5.35 (s,1H), 3.2 (t, 2H), 1.95-2.05 (m, 2H), 1.9 (s, 3H), 1.65-1.75 (m, 2H),1.5-1.6 (m, 2H), 1.25-1.35 (m, 2H); ¹³C NMR σ 171, 141, 121, 74 (t), 41,35, 31, 29, 24, 19; ³¹P NMR (single peak, not referenced).

[0128] The hydrolytic stability of Example 1 was demonstrated by agingin water for 5 months at 45° C. without any detectable hydrolysis (basedon ³¹P NMR) being observed.

Example 1A (1-Hydroxy-6-acrylamidohexylidene)bisphosphonic Acid (FormulaII: R³═H, R⁴═H, x=1, R²═OH, and A=(CH₂)₅)

[0129] (1-Hydroxy-6-acrylamidohexylidene)bisphosphonic acid (whitesolid, Example 1A) was prepared and characterized as described forExample 1, except that acryloyl chloride was substituted formethacryloyl chloride.

Example 2 (1-Hydroxy-4-methacrylamidobutylidene)bisphosphonic Acid(Formula II: R³═CH₃, R⁴═H, x=1, R²═OH, and A=(CH₂)₃)

[0130] Example 2 was prepared from Compound B by the same procedure asdescribed for Example 1. A white solid was isolated in 74.8% yield andwas characterized as (1-hydroxy-4-methacrylamidobutylidene)bisphosphonicacid (Example 2) having the following NMR values: ¹H NMR (D₂O) σ 5.55(s, 1H), 5.30 (s, 1H), 3.15 (t, 2H), 1.85-2.00 (m, 2H), 1.80 (s, 3H),1.70-1.80 (m, 2H);

[0131]¹³C NMR σ 172, 139, 121, 74 (t), 40, 31, 24, 18; ³¹P NMR σ 20.4(s)

Example 3 (1-Hydroxy-12-methacrylamidododecylidene)bisphosphonicAcid(Formula II: R³═CH₃, R⁴═H, x=1, R²═OH, and A=(CH₂)₁₁)

[0132] Potassium hydroxide pellets (19.75 g, 0.35 mol) were dissolved inwater (60 ml) in a 500 ml 2-neck flask equipped with a mechanicalstirrer. Compound C (20.0 g, 0.05 mol) was added and stirring wascontinued until a clear solution was obtained. The flask was cooled inan ice bath for 15 minutes. Methacryloyl chloride (5.90 g, 0.055 mol)was added dropwise to the cold solution with vigorous stirring over 10minutes. The mixture was stirred for 3 hours in the ice bath andconcentrated hydrochloric acid was added slowly and dropwise until themixture became acidic (about 21.5 mol of concentrated HCl were used).The separated solid was filtered by vacuum filtration. The filter cakewas washed several times with water and then air dried over night. Awhite solid was isolated in 90.85% yield and was determined to have ¹H,¹³C, and ³¹P NMR values (recorded using a KOH solution of the solid)consistent with the compound(1-hydroxy-12-methacrylamidododecylidene)bisphosphonic acid (Example 3).

Example 4 (1-Hydroxy-11-methacrylamidoundecylidene)bisphosphonic Acid(Formula II: R³═CH₃, R⁴═H, x=1, R²═OH, and A=(CH₂)₁₀)

[0133] Example 4 was prepared from Compound D by the same procedure asdescribed for Example 3. A white solid was isolated in 78.95% yield andwas determined to have ¹H, ¹³C, and ³¹P NMR values (recorded using a KOHsolution of the solid) consistent with the compound(1-hydroxy-11-methacrylamidoundecylidene)bisphosphonic acid (Example 4).

Example 5 (Methylidene Methanebisphosphonic Acid) (Formula I: R¹ and R²are CH₃CH═)

[0134] General Synthetic Procedure A

[0135] Tetraalkyl methanebisphosphonates react with aliphatic andaromatic aldehydes to produce tetraalkyl alkylidene and arylidenemethanebisphosphonates (Formula I where R¹ and R² form a double bondwith the central carbon of the P—C—P group and with alkyl groups on the4 P—OH groups). The resulting tetraalkyl alkylidene and arylidenemethanebisphosphonates can be hydrolyzed in acid to yield thecorresponding alkylidene and arylidene methanebisphosphonic acids.

[0136] Following the General Synthetic Procedure A, acetaldehyde isreacted with tetramethyl methanebisphosphonate to produce tetramethylmethylidene methanebisphosphonate that is then hydrolyzed to yieldmethylidene methanebisphosphonic acid. (Formula I where R¹ and R² form aCH₃CH═ link to the central carbon of the P—C—P group.)

Example 6 (4-Methacrylamidobutylidene Methanebisphosphonic Acid)(Formula I: R¹ and R² are CH₂═C(CH₃)C(O)NH(CH₂)₃CH═)

[0137] Following the General Synthetic Procedure A, 4-nitrobutanal isreacted with tetramethyl methanebisphosphonate to produce tetramethyl4-nitrobutylidene methanebisphosphonate that is then hydrogenated toreduce the nitro group to an amine group, and then hydrolyzed to yield4-aminobutylidene methanebisphosphonic acid. The resulting acid is thenmethacrylated with methacryloyl chloride to afford4-methacrylamidobutylidene methanebisphosphonic acid.

Example 7 (4-Vinylbenzyl-methanebisphosphonic Acid) (Formula I: R¹ is4-vinylbenzyl and R² is H)

[0138] General Synthetic Procedure B

[0139] Tetraalkyl methanebisphosphonates react with aliphatic andaromatic halides (e.g., chlorides, bromides, and iodides) to producetetraalkyl alkyl- and aryl-methanebisphosphonates (Formula I where R¹ isalkyl or aryl, R² is H, and with alkyl groups on the 4 P—OH groups). Theresulting tetraalkyl alkyl- and aryl-methanebisphosphonates can behydrolyzed in acid to yield the corresponding alkyl- andaryl-methanebisphosphonic acids.

[0140] Following the General Synthetic Procedure B,4-vinylbenzylchloride is reacted with tetramethyl methanebisphosphonateto produce tetramethyl 4-vinylbenzyl-methanebisphosphonate that is thenhydrolyzed to yield 4-vinylbenzyl-methanebisphosphonic acid.

Example 8 (6-Methacryloxyhexyl-methanebisphosphonic Acid) (Formula I: R¹is 6-methacryloxyhexyl and R² is H)

[0141] Following the General Synthetic Procedure B, methyl6-chlorohexanoate is reacted with tetramethyl methanebisphosphonate toproduce tetramethyl 5-methoxycarbonylpentyl-methanebisphosphonate thatis then hydrolyzed to yield 5-carboxypentyl-methanebisphosphonic acid,and then hydrogenated to reduce the carboxy group to a hydroxymethylenegroup. The resulting 6-hydroxyhexyl-methanebisphosphonic acid is thenmethacrylated with methacryloyl chloride to afford6-methacryloxyhexyl-methanebisphosphonic acid.

Example 9 (1,3-Bis(methacrylamido)butane-1,1-bisphosphonic Acid)(Formula II: R2 is NHCOCCH₃═CH₂, R³ is CH₃, R⁴ is H, and A is—CH(CH₃)CH₂—)

[0142] The starting material 1,3-diamino-butane-1,1-bisphosphonic acidcan be prepared by the reaction of 3-aminobutyronitrile withphosphorus-tribromide in dioxane followed by hydrolysis andcrystallization according to the following procedure.3-Aminobutyronitrile (21 g, 0.25 mol) is dissolved in 100 ml dioxane andis reacted with phosphorus-tribromide (135.5 g, 0.5 mol) at 30° C. for24 hours. Water is added (27 g, 1.5 mol) and the mixture is heated to65° C. for 3 hours. After addition of 100 g water, dioxane is distilledoff, and the product (1,3-diaminobutane-1,1-bisphosphonic acid)crystallizes from the residue during cooling to 20° C. After separationby filtration, the product is washed several times with small amounts ofcold water and then dried in a vacuum at 110° C.

[0143] Yield 9.1 g (15% theory). Melting point 255° C.

[0144] Example 9 (1,3-bis(methacrylamido)butane-1,1-bisphosphonic Acid)can be prepared by the reaction of 1,3-diaminobutane-1,1-bisphosphonicacid with methacryloyl chloride according to the following procedure.Sodium hydroxide pellets (28.0 g, 0.70 mol) are dissolved in water (90ml) in a 250-ml 2-neck flask equipped with a mechanical stirrer. Theresulting solution is cooled in an ice bath for 15 minutes. Withvigorous stirring, 1,3-diaminobutane-1,1-bisphosphonic acid (24.81 g,0.100 mol) is added and the resulting mixture is stirred for one hour.To the cold solution is added methacryloyl chloride (23.0 g, 0.220 mol)dropwise over 10 minutes. The mixture is vigorously stirred in the icebath for 3 hours. The mixture is acidified using concentrated HCl untilpH paper indicates a pH value below 2. Methanol (300 ml) is added andthe resulting solid precipitate is removed by filtration. The filtrateis concentrated in a rotary evaporator and the residue is dissolved inmethanol (120 ml). The solution is filtered again and the filtrate isconcentrated in a rotary evaporator to afford solid that is dried undervacuum. The dried solid is characterized as1,3-bis(methacrylamido)butane-1,1-bisphosphonic acid (Example 9).

Examples 10-13 Compositions and Evaluations

[0145] The compositions of the present invention were prepared by thefollowing general procedure. A solid bisphosphonic acid derivative(e.g., Example 1 or 1A) was first weighed into a clear glass vialfollowed by the addition of water, optionally a polymerizable component,and optionally other ingredients, such as, additional polymerizablecomponents, surfactants, salts, and initiators. Once all of thecomponents had been added, the vial was tightly capped and vigorouslyshaken by hand for about 30 seconds. Based on visual observations, theresulting compositions were clear, homogeneous solutions. Followingmixing, the compositions were transferred into an opaque vial forevaluation according to the Shear Bond Strength Test Method describedherein.

[0146] The compositions prepared in this manner are listed in Table 1along with the optional adhesives utilized in the Test Method and theresults obtained for shear bond strength to enamel and dentin. Negativecontrols were run for comparison and included SINGLEBOND Adhesive only(Control 1) and SCOTCHBOND Multipurpose Plus Adhesive only (Control 2).The results of these two Controls showed relatively low adhesion foradhesives applied to an enamel or dentin surface that had not beentreated with an etchant-containing material. Example 12 is noted as anexample of a self-etching adhesive composition, in that it was used asboth an etchant and an adhesive to treat the tooth surface before curingand adherence of the composite material.

Tooth Surface Evaluation by Scanning Electron Microscopy (SEM)

[0147] Selected bisphosphonic acid derivatives of the present inventioncould be shown by Scanning Electron Microscopy (SEM) to etch the enamelsurface of a tooth. For example, the self-etching primer compositionExample 11 was applied to an enamel tooth surface prepared using320-grit sandpaper. The composition was allowed to remain for 20 secondsand then rinsed off the surface with distilled water. The tooth surfacewas dried and scanned using standard SEM techniques. The SEM imageshowed an etched pattern on the treated enamel. TABLE 1 Shear BondStrength Primer Composition Adhesive (Applied (MPa) Ex. Component Wt.-%After Primer) Enamel Denim 10 Example 1 7.5 SINGLEBOND 27.7 ± 2.3 11.9 ±4.0 HEMA 42.5 Adhesive Water 50 (3M Company) 11 Example 1 7.5 SCOTCHBOND34.2 ± 3.6  3.0 ± 1.5 PEGDMA 400 5 Multipurpose Plus HEMA 37.5 AdhesiveWater 50 (3M Company) 12 Example 1 7.5 None 23.4 ± 6.7  2.2 ± 2.2 PEGDMA400 5 HEMA 45.5 CPQ 0.8 EDMAB 0.65 DPIHFP 0.55 Water 40 13 Example 1A7.5 SINGLEBOND 20.4 ± 5.6  7.5 ± 3.9 HEMA 42.5 Adhesive Water 50 ControlNone — SINGLEBOND  4.3 ± 1.4  2.2 ± 2.6 1 Adhesive Control None —SCOTCHBOND  6.5 ± 0.9  0.6 ± 0.9 2 Multipurpose Plus Adhesive

[0148] The complete disclosures of the patents, patent documents, andpublications cited herein are incorporated by reference in theirentirety as if each were individually incorporated. Variousmodifications and alterations to this invention will become apparent tothose skilled in the art without departing from the scope and spirit ofthis invention. It should be understood that this invention is notintended to be unduly limited by the illustrative embodiments andexamples set forth herein and that such examples and embodiments arepresented by way of example only with the scope of the inventionintended to be limited only by the claims set forth herein as follows.

What is claimed is:
 1. An etching composition comprising: apolymerizable component; and a compound of Formula I, which is differentfrom the polymerizable component, wherein Formula I is:

or a salt thereof, wherein: R¹ is an organic group that includes apolymerizable group; and R² is H, OR, SR, N(R)₂, or an organic groupthat can optionally join with R¹ to form a carbon-carbon double bondwith the carbon between the two phosphorus atoms, wherein the organicgroup optionally includes a polymerizable group, and further whereineach R is independently hydrogen or an organic group optionallyincluding a polymerizable group; wherein the compound of Formula I ispresent in an amount sufficient to etch a hard surface, thereby formingan etchant.
 2. An etching composition comprising: a polymerizablecomponent; and a compound of Formula II, which is different from thepolymerizable component, wherein Formula II is:

or a salt thereof, wherein: x=1-3; R² is H, OH, an alkyl group, an arylgroup, an alkoxy group, an aryloxy group, or-A-(N(R⁴)—C(O)—C(R³)═CH₂)_(x); each R³ is independently H or CH₃; eachR⁴ is independently H, an alkyl group, or can be joined to A forming acyclic organic group; and A is a straight chain or branched organicgroup; wherein the compound of Formula II is present in an amountsufficient to etch a hard surface, thereby forming an etchant.
 3. Thecomposition of claim 2 wherein the composition is a self-etching primer.4. The composition of claim 2 wherein the composition is a self-etchingadhesive.
 5. The composition of claim 2 wherein each R⁴ is independentlya (C1-C4)alkyl group.
 6. The composition of claim 2 wherein each R⁴ isindependently H.
 7. The composition of claim 2 wherein R² is a(C1-C4)alkoxy group.
 8. The composition of claim 2 wherein R² is OH. 9.The composition of claim 2 wherein A is (CH₂)_(n) wherein n=1-20. 10.The composition of claim 9 wherein n=3-11.
 11. The composition of claim10 wherein n=5.
 12. The composition of claim 2 wherein the compound ofFormula II is present in an amount of at least about 1 wt-%, based onthe total weight of the composition.
 13. The composition of claim 2wherein the polymerizable component is selected from the groupconsisting of ethylenically unsaturated compounds.
 14. The compositionof claim 2 wherein the polymerizable component is selected from thegroup consisting of 2-hydroxyethyl methacrylate (HEMA),polyethyleneglycol dimethacrylate (PEGDMA), copolymer of acrylicacid:itaconic acid with pendent methacrylate (AA:ITA:IEM),2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy)phenyl]propane (bisGMA),urethane dimethacrylate (UDMA), and glycerol dimethacrylate (GDMA), andcombinations thereof.
 15. The composition of claim 2 further comprisingan adhesive component.
 16. The composition of claim 2 further comprisinga primer component.
 17. The composition of claim 2 further comprising afiller.
 18. The composition of claim 2 further comprising water or anonaqueous solvent.
 19. The composition of claim 2 further comprising aphotoinitiator.
 20. The composition of claim 2 further comprising anoxidizing agent and a reducing agent.
 21. The composition of claim 2wherein the hard surface is dentin or enamel.
 22. A compositioncomprising: a polymerizable component; and a compound of Formula I,which is different from the polymerizable component, wherein Formula Iis:

or a salt thereof, wherein: R¹ is an organic group that includes apolymerizable group; and R² is H, OR, SR, N(R)₂, or an organic groupthat can optionally join with R¹ to form a carbon-carbon double bondwith the carbon between the two phosphorus atoms, wherein the organicgroup optionally includes a polymerizable group, and further whereineach R is independently hydrogen or an organic group optionallyincluding a polymerizable group; wherein the compound of Formula I ispresent in an amount of at least about 1 wt-%, based on the total weightof the composition.
 23. A composition comprising: a polymerizablecomponent; and a compound of Formula II, which is different from thepolymerizable component, wherein Formula II is:

or a salt thereof, wherein: x=1-3; R² is H, OH, an alkyl group, an arylgroup, an alkoxy group, an aryloxy group, or-A-(N(R⁴)—C(O)—C(R³)═CH₂)_(x); each R³ is independently H or CH₃; eachR⁴ is independently H, an alkyl group, or can be joined to A forming acyclic organic group; and A is a bond or a straight chain or branchedorganic group; wherein the compound of Formula II is present in anamount of at least about 1 wt-%, based on the total weight of thecomposition.
 24. The composition of claim 23 wherein the composition isan etchant for a hard surface.
 25. The composition of claim 23 whereinthe composition is a self-etching primer.
 26. The composition of claim23 wherein the composition is a self-etching adhesive.
 27. Thecomposition of claim 23 wherein each R⁴ is independently a (C1-C4)alkylgroup.
 28. The composition of claim 23 wherein each R⁴ is H.
 29. Thecomposition of claim 23 wherein R² is a (C₁-C₄)alkoxy group.
 30. Thecomposition of claim 23 wherein R² is OH.
 31. The composition of claim23 wherein A is (CH₂)_(n) wherein n=1-20.
 32. The composition of claim31 wherein n=3-11.
 33. The composition of claim 32 wherein n=5.
 38. Thecomposition of claim 23 wherein the compound of Formula II is present inan amount of at least about 5 wt-%, based on the total weight of thecomposition.
 39. The composition of claim 23 wherein the polymerizablecomponent is selected from the group consisting of ethylenicallyunsaturated compounds.
 40. The composition of claim 39 wherein thepolymerizable component is selected from the group consisting of HEMA,PEGDMA, AA:ITA:IEM, bisGMA, UDMA, GDMA, and combinations thereof. 41.The composition of claim 23 for bonding a dental restorative to a hardsurface.
 42. The composition of claim 41 wherein the hard surface isdentin or enamel.
 43. The composition of claim 23 further comprising anadhesive component.
 44. The composition of claim 23 further comprising afiller.
 45. The composition of claim 23 further comprising water or anonaqueous solvent.
 46. A method of treating a hard surface, the methodcomprising: etching the hard surface with a composition comprising acompound of the following Formula I:

or a salt thereof, wherein: R¹ is an organic group that includes apolymerizable group; and R² is H, OR, SR, N(R)₂, or an organic groupthat can optionally join with R¹ to form a carbon-carbon double bondwith the carbon between the two phosphorus atoms, wherein the organicgroup optionally includes a polymerizable group, and further whereineach R is independently hydrogen or an organic group optionallyincluding a polymerizable group; with the proviso that the hard surfaceis not pretreated.
 47. A method of treating a hard surface, the methodcomprising: etching the hard surface with a composition comprising acompound of the following Formula II:

or a salt thereof, wherein: x=1-3; R² is H, OH, an alkyl group, an arylgroup, an alkoxy group, an aryloxy group, or-A-(N(R⁴)—C(O)—C(R³)═CH₂)_(x); each R³ is independently H or CH₃; eachR⁴ is independently H, an alkyl group, or can be joined to A forming acyclic group; and A is a bond or a straight chain or branched organicgroup; with the proviso that the hard surface is not pretreated.
 48. Themethod of claim 47 wherein the composition etches and primes the hardsurface.
 49. The method of claim 48 wherein the hard surface is a hardtissue.
 50. A method of treating a tooth surface, the method comprising:etching the tooth surface with a composition comprising a compound ofthe following Formula I:

or a salt thereof, wherein: R¹ is an organic group that includes apolymerizable group; and R² is H, OR, SR, N(R)₂, or an organic groupthat can optionally join with R¹ to form a carbon-carbon double bondwith the carbon between the two phosphorus atoms, wherein the organicgroup optionally includes a polymerizable group, and further whereineach R is independently hydrogen or an organic group optionallyincluding a polymerizable group; with the proviso that the tooth surfaceis not pretreated with phosphoric acid.
 51. A method of treating a toothsurface, the method comprising: etching the tooth surface with acomposition comprising a compound of the following Formula II:

or a salt thereof, wherein: x=1-3; R² is H, OH, an alkyl group, an arylgroup, an alkoxy group, an aryloxy group, or-A-(N(R⁴)—C(O)—C(R³)═CH₂)_(x); each R³ is independently H or CH₃; eachR⁴ is independently H, an alkyl group, or can be joined to A forming acyclic organic group; and A is a bond or a straight chain or branchedorganic group; with the proviso that the tooth surface is not pretreatedwith phosphoric acid.
 52. The method of claim 51 wherein the compositionfurther comprises at least one polymerizable component different fromthe compound of Formula II.
 53. The method of claim 52 wherein thecomposition functions as a self-etching primer thereby etching andpriming the tooth surface simultaneously.
 54. The method of claim 52wherein the composition functions as a self-etching adhesive to promoteadherence of a dental material to the tooth surface.
 55. The method ofclaim 54 wherein the dental material is selected from the groupconsisting of a composite, a filling, a sealant, an inlay, an onlay, acrown, and a bridge.
 56. The method of claim 52 wherein the compositionfunctions to promote the adherence of an orthodontic adhesive to thetooth surface, wherein the orthodontic adhesive functions to adhere anorthodontic appliance to the tooth surface.
 57. The method of claim 56wherein the orthodontic appliance is selected from the group consistingof a bracket, a buccal tube, a band, a cleat, a button, a lingualretainer, and a bite blocker.
 58. The method of claim 51 furthercomprising a step of priming the tooth surface.
 59. The method of claim51 further comprising a step of applying a dental adhesive to the toothsurface.
 60. The method of claim 51 wherein the tooth surface comprisesenamel.
 61. The method of claim 51 wherein the tooth surface comprisesdentin.
 62. A method of adhering an orthodontic appliance to a toothsurface, the method comprising: etching the tooth surface with acomposition comprising a compound of the following Formula I:

or a salt thereof, wherein: R¹ is an organic group that includes apolymerizable group; and R² is H, OR, SR, N(R)₂, or an organic groupthat can optionally join with R¹ to form a carbon-carbon double bondwith the carbon between the two phosphorus atoms, wherein the organicgroup optionally includes a polymerizable group, and further whereineach R is independently hydrogen or an organic group optionallyincluding a polymerizable group; and adhering an orthodontic applianceto the tooth surface.
 63. A method of adhering an orthodontic applianceto a tooth surface, the method comprising: etching the tooth surfacewith a composition comprising a compound of the following Formula II:

or a salt thereof, wherein: x=1-3; R² is H, OH, an alkyl group, an arylgroup, an alkoxy group, an aryloxy group, or-A-(N(R⁴)—C(O)—C(R³)═CH₂)_(x); each R³ is independently H or CH₃; eachR⁴ is independently H, an alkyl group, or can be joined to A forming acyclic organic group; and A is a bond or a straight chain or branchedorganic group; and adhering an orthodontic appliance to the toothsurface.
 64. The method of claim 63 further comprising adhering anorthodontic adhesive to the tooth surface.
 65. The method of claim 64wherein the orthodontic adhesive has been pre-applied to the orthodonticappliance before adhering to the tooth surface.
 66. The method of claim63 wherein the orthodontic appliance is selected from the groupconsisting of a bracket, a buccal tube, a band, a cleat, a button, alingual retainer, and a bite blocker.
 67. The method of claim 63 furthercomprising a step of priming the tooth surface prior to adhering anorthodontic appliance to the tooth surface.
 68. The method of claim 67wherein the composition further comprises at least one polymerizablecomponent different from the compound of Formula II and wherein thesteps of etching and priming are done simultaneously with thecomposition functioning as a self-etching primer composition.
 69. Themethod of claim 68 further comprising adhering an orthodontic adhesiveto the tooth surface.
 70. The method of claim 69 wherein the orthodonticadhesive has been pre-applied to the orthodontic appliance beforeadhering to the tooth surface.
 71. The method of claim 63 furthercomprising a step of applying a dental adhesive to the tooth surfaceprior to adhering an orthodontic appliance to the tooth surface.
 72. Themethod of claim 71 wherein the composition further comprises at leastone polymerizable component different from the compound of Formula IIand wherein the steps of etching and applying a dental adhesive are donesimultaneously with the composition acting as a self-etching adhesivecomposition.
 73. The method of claim 72 further comprising adhering anorthodontic adhesive to the tooth surface.
 74. The method of claim 73wherein the orthodontic adhesive has been pre-applied to the orthodonticappliance before adhering to the tooth surface.